Mechanisms of protective immunity were studied in mice resistant to challenge with Schistosoma mansoni as a result of vaccination with radiation attenuated cercariae. Previous studies in our laboratory had indicated that vaccinated mice develop low levels of antibody and T cell responses which wane with time. We showed this year that challenge infection of previously vaccinated animals results in dramatic anamnestic B and T lymphocyte responses as measured by anti-larval antibody titer and lymphocyte proliferation. Thus, vaccination induces a potent immunologic memory which is recalled by challenge infection. In a related study, vaccination was shown to result in the induction of T cells which upon in vitro exposure to schistosomulum antigens produce lymphokines capable of activating macrophages to kill these larvae. Indeed, these activated macrophages could be elicited in vivo by intraperitoneal injection of mice with schistosomula. The lymphokine mediating macrophage activation was characterized by Sephadex gel filtration as possessing an approximate molecular weight of 50,000 and was found to contain gamma interferon activity. A mouse strain P/N was identified which fails to develop resistance to challenge as a result of vaccination. Analysis of vaccinated P/N mice revealed that they failed to produce normal levels of delayed type hypersensitivity to schistosomulum antigens, and were defective in both antigen induced lymphokine production and macrophage activation. Furthermore, these mice produced lower levels of IgM anti-larval antibodies than did mouse strains developing high levels of vaccine induced resistance (e.g. B/6). Preliminary results of genetic crosses between P/N and B/6 mice indicated that the defects in vaccine induced resistance and humoral and cell mediated immunity in P/N mice are inherited as recessive traits and that there is a correlation between resistance and antibody response in backcross animals.